A novel exercise testing algorithm to diagnose mitochondrial myopathy

Abstract

Introduction: Oxygen uptake efficiency slope (OUES) is a noninvasive cardiopulmonary exercise testing (CPET) measurement based on oxygen uptake (V˙O₂ ) and minute ventilation (V˙E) and is a marker of the efficiency of oxygen utilization by the body. However, it has not been studied in mitochondrial disorders. We explored noninvasive CPET parameters, including OUES, as a way to reliably diagnose mitochondrial myopathy.

Methods: We performed cycle ergometer maximal exercise testing on definite and suspected mitochondrial myopathy subjects (MM-D and MM-S) and their age- and sex-matched controls. OUES was corrected for body surface area (OUES/BSA) to eliminate the effect of body size.

Results: A total of 40 participants, including 20 MM-D (n = 13; 6 males; aged 14-64 years) and 7 MM-S (5 males, aged 11-30 years) subjects and 20 controls, completed the study. MM-D subjects showed lower aerobic fitness than controls. OUES/BSA was lower in MM-D subjects, suggesting inefficient oxygen utilization. Area under the curve (AUC) and 95% confidence interval (CI) for OUES/BSA (AUC, 0.91; 95% CI, 0.80-1.00), peak V˙O₂ percent predicted (AUC, 0.95; 95% CI, 0.86-1.00), and V˙O₂ /work slope (AUC, 0.94; 95% CI, 0.85-1.00) showed excellent ability to diagnose mitochondrial myopathy in MM-D subjects. We applied a diagnostic approach based on the parameters just noted to MM-S subjects and their controls and were able to support or disprove the diagnosis of mitochondrial myopathy.

Discussion: We proposed and applied an approach based on the aformentioned three CPET parameters to diagnose mitochondrial myopathy reliably and found it to be clinically useful.

Keywords: V˙O2/work slope; cardiopulmonary exercise testing; mitochondrial myopathy; oxygen uptake; oxygen uptake efficiency slope.